Genetic variation is the fundamental basis of inherited disease and acquired diseases such as cancer. Current technologies allow us to investigate diseases where only one or a small number of variants of genes are altered e.g CF or Huntingtons disease. With inherited nephrotic syndrome (NS) it is now known that at least several dozen different genes could be altered, and we know almost nothing about how different alterations affect disease severity or response to treatment.
Recent advances in sequencing technologies are likely to revolutionalize medical diagnostics in both inherited and acquired disease. Using massively parallel sequencing – otherwise known as Next Generation Sequencing, and ever advancing bioinformatics platforms, we can now reliably sequence and analyse huge portions of the human genome. These platforms generate data on all the genetic variation potentially associated with NS, leading to the isolation of novel genes. The University of Bristol has one of these platforms, the Illumina GA2 within its genome research facility.
A key component of understanding the genetic basis of disease is a tightly defined and phenotyped cohort of patients. The project seeks to evaluate the application of targeted Next Generation sequencing technology to acquired and inherited NS gene pathways using such a cohort of patients, carefully collected as part of RADAR, the newly established renal rare disease registry (1-2). We aim to assess the quality of genetic data generated by the technique, the extent of genetic variation in patients with NS, the utility of current bioinformatics packages/databases in assigning pathogenic /benign genetic variant status, the number of patients where NGS has highlighted a potential genetic cause of NS and potential new candidate genes. This work will further the knowledge of genetic pathways of NS and contribute to the development of improved genetic testing and individualised management for patients with these diseases
When applying please select ’Medicine PhD’ within the Faculty of Health Sciences.
(1) Ding, W.Y., Koziell, A., McCarthy, H.J., Bierzynska, A., Bhagavatula, M.K., Dudley, J.A., Inward, C.D., Coward, R.J., Tizard, J., Reid, C., Antignac, C., Boyer, O., & Saleem, M.A. (2014) Initial steroid sensitivity in children with steroid-resistant nephrotic syndrome predicts post-transplant recurrence. J Am Soc Nephrol. 25 1342-8
(2) McCarthy, H.J., Bierzynska, A., Wherlock, M., Ognjanovic, M., Kerecuk, L., Hegde, S., Feather, S., Gilbert, R.D., Krischock, L., Jones, C., Sinha, M., Webb, N., Christian, M., Marks, S., Koziell, A., Welsh, G.I. & Saleem, M.A. (2013) Simultaneous sequencing of 24 genes associated with steroid resistant nephrotic syndrome, harnessing Next Generation Sequencing. Clinical Journal of the American Society of Nephrology. 8:637-648.